
Aryloxypropylamines are an important class of pharmaceutical products used in the care of attention-deficit disorder and hyperactivity disturbances.
Some of the most important products belonging to this class are the following:

Duloxetine is a chemically very similar product having the following formula:

It is used as drug for the care of depression and incontinence.
The known synthesis paths for obtaining this product type starting from the corresponding amino alcohol can be divided into two groups:
A) Aromatic nucleophilic substitution processes like those described in WO0058262.
This hind of process provides for the substitution of a halogen atom on the ring by the OH of the amino alcohol of formula II, suitably activated as an alcoholate. This process type is applicable with good results only when electron-attractor groups are present on the aromatic ring which bears the halogen to be substituted (in the diagram below, when A and X have the meanings defined above and Y′ is an electron-attractor group).
B) Nucleophilic substitution reactions of the hydroxyl of the amino alcohol. (see for example U.S. Pat. No. 4,018,895 and U.S. Pat. No. 4,314,081).
This kind of process normally provides for the following reaction sequence:
a) protection of the amino group;
b) activation of the hydroxyl by means of its transformation into a good leaving group (preferably a halogen);
c) nucleophilic substitution with the appropriate aryloxy, optionally substituted;
d) deprotection of the amino group

The processes of this type are longer but have a much wider range of application.